This review concluded that condom use offered moderate protection against herpes simplex virus 2 (HSV-2) acquisition in men and women. A number of problems with the conduct and reporting of the review process mean that it is difficult to determine the reliability of this conclusion.

Authors' objectives

To assess the effectiveness of condom use in preventing the transmission of herpes simplex virus 2.

Searching

PubMed was searched up to 2007. Search terms were reported. Researchers in the field were also contacted to identify additional studies.

Study selection

Prospective cohort studies in which participants were tested with type-specific herpes simplex virus 2 (HSV-2) antibody tests at baseline and follow-up were eligible for inclusion. Studies were required to assess both condom use and frequency of sexual activity throughout the study and to provide laboratory documentation of HSV-2 acquisition. Laboratory documentation was defined as use of culture analysis, polymerase chain reaction assay or type-specific serologic analysis.

Included studies were HSV-2 vaccine studies, HSV-2 drug studies, observational studies of sexually transmitted infections and behavioural interventions for human immunodeficiency virus (HIV). Placebo arms only were included for some studies. All studies included safer sex counselling as part of their follow-up. Participants in included studies were mainly heterosexual (94%), had a mean age of 29 years, 66% were male, 60% were HSV-1 sero-positive at baseline, and the majority reported no previous sexually transmitted infections.

The authors did not state how the papers were selected for the review, or how many reviewers performed the selection.

Assessment of study quality

The authors did not state that they assessed validity.

Data extraction

Authors were contacted for individual level data. Data were standardised across the studies. Where categories of condom use frequency were reported, the corresponding percentages were obtained from the study questionnaire and the midpoint used in analyses which assessed condom use as a continuous variable. Only data on participants known to be herpes simplex virus 2 (HSV-2) negative at baseline were included. Data on participants who reported no sexual activity, or were not tested for HSV-2 or interviewed about condom use during the follow-up period, were also not included. For missing data, data from visits up to six months previously were carried forward.

Race data were obtained from the original studies and categorised as "African-American", "white" or "other". HSV-2 acquisition was dated to the midpoint between the last negative and the first positive test dates. Continuous measures of behaviour were averaged over all time points before a study summary statistic was calculated. The authors did not state how many reviewers carried out the data extraction.

Methods of synthesis

Studies were combined using stratified univariate Cox regression models to calculate hazard ratios with 95% confidence intervals (CI) for each risk factor, including condom use; the following categorical variables were incorporated: number of genital or anal sex acts per week, age, gender, sexually transmitted disease history, baseline herpes simplex virus 1 status, sexual orientation, and monogamy (based on whether the study was a couples study, as well as reported partner numbers). Condom use was included as a continuous variable: the percentage of sex acts during which a condom was used. The aggregate effect of condoms for every 25% increase in use was assessed though multiplication of coefficients; gender and study were included as interaction terms. Adjusted models which accounted for the number of sex acts per week were generated using the Hosmer and Lemeshow stepwise method. A multivariate model was then developed which included the variables of age, gender, race and sex acts per week. Frequency of unprotected sex acts was calculated using the data on sex act and condom use frequency.

Results of the review

Six studies (n=5,384 individuals who were herpes simplex virus 2 negative at baseline) were included in the study, with 475 excluded for a priori specified reasons. A total of 2,040,894 follow-up days were included, with a median follow-up of 374 days (range four to 987 days). A total of 415 individuals acquired herpes simplex virus 2 (HSV-2) during follow-up, with a incidence of 7.4 per 100 person years(95% confidence interval (CI): 6.7 to 8.2). However, there was considerable variation between studies (range 5.1 to 16.2 per 100 person years).

The association between a 25% increase in condom use and HSV-2 acquisition was not statistically significant in the univariate model (hazard ratio 0.95, 95% CI: 0.88 to 1.00; p = 0.09). The multivariate model showed a significant decrease in risk of HSV-2 acquisition with a 25% increase in condom use (hazard ratio 0.93, 95% CI: 0.85 to 0.99; p = 0.01) while the aggregate hazard ratio for 100% versus 0% condom use was 0.70 (95% CI: 0.40 to 0.94).

There was an increased adjusted hazard ratio of HSV-2 acquisition (1.16, 95% CI: 1.08 to 1.25; p<0.001) for increasing numbers of unprotected sex acts per week.

No analysis showed a significant interaction effect for study or gender.

The review question and the inclusion criteria were clear, although studies which examined other interventions such as vaccines, from which only placebo group data were included, were also permitted. The authors searched only one database, which increased the risk that some relevant studies were not included in the review. The risk of publication and language bias was also unclear. Although experts were contacted, no systematic search for unpublished studies was reported. It is also unclear if language restrictions were applied. The authors did not report assessing the validity of the included studies, nor did they report using methods designed to reduce reviewer bias and error at any stage of the review process. The use of regression analyses to assess the relationship between condom use and HSV-2 acquisition appeared to be reasonable. The authors' conclusions reflected the results of these analyses. However, the pooling of subsets of data from studies which are clinically and methodologically heterogeneous, and which varied considerably in study objectives, may not have been appropriate. Given the limited search, the poor reporting of the review process, the lack of an assessment of validity, and the nature of the included data, it is difficult to determine the reliability of the authors' conclusions.

Implications of the review for practice and research

The authors did not state any implications for practice or further research.

Funding

National Institutes of Health, National Institute of Allergy and Infectious Diseases, grant numbers P01 AI-030731 and K24 A1-107113.

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.